Field of the Disclosure
Embodiments of the present invention relate to a two part, curable composition, methods for preparing the composition, manufacture thereof and methods for sterilisation thereof, medical and non-medical use thereof, methods for use or therapy therewith, a device incorporating the composition, and a precursor therefor including its sterilisable precursor composition. In particular certain embodiments relate to a sterilisable or sterile composition for medical use, particularly in wound therapy, more particularly as a wound packing material or filler which can be shaped and configured to the shape of a wound, or an adhesive or sealant for a wound dressing, most particularly for application in negative pressure wound therapy (NPWT).
Background
NPWT is a relatively new treatment for open wounds. Briefly, negative pressure therapy can assist in the closure and healing of many forms of “hard to heal” wounds by reducing tissue oedema; encouraging blood flow and granular tissue formation; removing excess exudate and may reduce bacterial load (and thus infection risk). In addition, the therapy allows for less disturbance of a wound leading to more rapid healing. TNP therapy systems may also assist on the healing of surgically closed wounds by removing fluid and by helping to stabilise the tissue in the apposed position of closure. A further beneficial use of TNP therapy can be found in grafts and flaps where removal of excess fluid is important and close proximity of the graft to tissue is required in order to ensure tissue viability. Typically in NPWT the wound cavity or surface is filled or covered with a material that allows the transmission of a partial vacuum (i.e. does not completely collapse) to the wound bed when a negative pressure is applied to the wound area, and also allows fluids to pass from the wound bed towards the source of negative pressure. There are two primary approaches to NPWT, i.e. gauze or foam types. The gauze type involves the use of a drain wrapped in gauze topped by a sealed dressing. The foam type involves the use of foam placed over or in the wound, also topped by a sealed dressing. One embodiment is directed primarily towards the foam type of NPWT. Further embodiments are directed towards either the foam or gauze type of NPWT, or to a further type of NPWT which uses a sealed dressing as a combination or preformed with additional absorption or distribution layers or the like.
A good material the foam based NPWT which offers good resistance to compression under loading, is hydrophobic, reticulated polyurethane foam of high free internal volume.
However articles of high free internal volume tend to be poorly drapeable due to the requirement for their structure to mechanically support their high free internal volume, and this is the case in foams applied in NPWT.
Therefore packing material for use in NPWT must be shaped to fit the wound to be packed. This is typically achieved by the medical practitioner (physician or nurse) cutting a preformed block of foam to approximately fit the wound using a scalpel, knife or scissors. This operation can be complex and has the potential to introduce contamination, moreover is time consuming and messy for the medical practitioner, and indeed can be dangerous with the possibility of particulate foam contaminating the wound site or of an accident during the cutting process. Accordingly the process of shaping the wound dressing is currently an unaddressed problem in the field of NPWT.
Castable compositions are known for use in wound care. WO2009/156709 discloses a topical negative pressure, or vacuum, wound therapy wound covering element or drape constructed of silicone or polyurethane based materials, which provides a substantially air-tight seal over a wound, having a vacuum connection tube or line for connection to a negative pressure source moulded or glued in place to reduce the likelihood of negative pressure leakage. The drape may be manufactured by casting a two-part heat curable silicone elastomer over the vacuum line, located in a mould. The resulting drape may be sterilised by irradiation and packaged in sterile form until required for use by placing over a foam or gauze wound filler.
An RTV-2 (addition cure two-part room temperature vulcanizing) silicone foam wound dressing, Cavi-Care, is sold non-sterile. U.S. Pat. No. 5,153,231 discloses the composition which is capable of providing a low density foamed medical dressing by releasing two components into a mixing vessel by rupture of their individual packaging, mixing and dispensing or casting onto a surface such as an open wound and allowing the mixture to cure at room temperature.
It would be useful to provide a castable in-situ wound filler in the form of an RTV-2 silicone foam. It would also be useful to provide a castable in-situ adhesive or sealant for a NPWT drape or dressing. The problem is that for an RTV-2 wound filler, adhesive, sealant or the like to be viable the two part system must be available sterile.
Where a product for medical use is required to be sterile at point of use, it is a well accepted principle that it should be manufactured using aseptic processing only when terminal sterilisation is not feasible. To ensure the highest levels of sterility assurance for a medical product, it should therefore be terminally sterilised in its final packaging.
Although sterile foamed wound dressing materials are available such as Allevyn™, a polyurethane foam wound covering element, and black foam (“Granufoam”), a polyurethane wound filler, supplied packaged in a peel pouch, no two-part RTV-2 silicone composition or indeed any RTV-2 composition, foamable or otherwise, appears to be available sterile, as the two part system prior to curing, either terminally sterilised in primary packaging or sterilised and then aseptically packaged. Furthermore a process for sterilising these systems does not appear to be available.
One object of the invention is to provide an improved terminally sterile RTV-2 foamable silicone composition. It is a further object to provide an improved, terminally sterile, wound filler which can be conformed to the shape of a wound cavity. It is a further object to provide a terminally sterile RTV-2 non-foamable or partially foamable silicone composition. It is a further object to provide a terminally sterile adhesive or sealant which can be conformed about a wound cavity.
In attempting to find a route to sterilise a two part foamable curable silicone composition which could be cast into a desired shape and cured in situ to form a shaped three dimensional body, we found that most of the sterilisation techniques that would be typically employed to sterilise a material are unsuitable or are incapable of sterilising the composition without degradation. The same was true in attempting to find a route to sterilise a two part adhesive or sealant.
Established terminal sterilisation procedures give a 106 confidence in sterility. An attractive route for sterilisation appeared to be irradiation. This presents a cost-effective route for which requisite packaging is readily available.
25 kGy is a typical dose for achieving the required level of microbial kill for terminal sterility. However on gamma irradiating at 25 kGy, Rhodorsil RTFoam 3240, a RTV-2 polydiorganosiloxane composition having liquid prepolymer mixture Part A and Part B, suffered a noticeable increase in viscosity in Part A whilst Part B formed a solid elastomer. The resulting sterile composition was clearly incapable of mixing and casting.
This viscosity increase can be influenced by reducing the gamma irradiation dose levels to 15 kGy and even 10 kGy, however across a wide range of gamma doses the irradiation alters the physical properties of the composition Part, with an increase in viscosity being observed at all dose levels.